Define Mesenchymal Stem Cell from Its Fate: Biodisposition of Human Mesenchymal Stem Cells in Normal and Concanavalin A-Induced Liver Injury Mice

doi:10.1124/jpet.121.000607

	Define Mesenchymal Stem Cell from Its Fate: Biodisposition of Human Mesenchymal Stem Cells in Normal and Concanavalin A-Induced Liver Injury Mice
	Han, Li 1,2; Ma, Chenhui 1,2; Peng, Huige 2; Wu, Zhitao 2,5; Xu, Huiming 3; Wu, Jiajun 1,2; Zhang, Ning 2; Jiang, Qinghui 1,2; Ma, Chen 1,2; Huang, Ruimin 1,2
刊名	JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
	2021-11-01
卷号	379 期号:2 页码:125-133
ISSN号	0022-3565
DOI	10.1124/jpet.121.000607
通讯作者	Li, Hai(haili_17@126.com) ; Pan, Guoyu(gypan@simm.ac.cn)
英文摘要	The pharmaceutical industry and clinical trials have been revolutionized mesenchymal stem cell-based therapeutics. However, the pharmacokinetics of transplanted cells has been little characterized in their target tissues under healthy or disease condition. A quantitative polymerase chain reaction analytical method with matrix effect was developed to track the biodistribution of human mesenchymal stem cells in normal mice and those with Concanavalin A (Con A)-induced liver injury. Mesenchymal stem/stromal cell (MSC) disposition in blood and different organs were compared, and relevant pharmacokinetic parameters were calculated. Human MSCs (hMSCs) and mouse MSCs (mMSCs) displayed a very similar pharmacokinetic profile in all tested doses: about 95% of the detected hMSCs accumulated in the lung and 3% in the liver, and almost negligible cells were detected in other tissues. A significant double peak of hMSC concentration emerged in the lung within 1-2 hours after intravenous injection, as with mMSCs. Prazosin, a vasodilator, could eliminate the second peak in the lung and increase its C-max and area under the concentration-time curve (AUC) by 10% in the first 2 hours. The injury caused by Con A was significantly reduced by hMSCs, and the C-max and AUC(0-8) (AUC from time 0 to 8 hours) of cells in the injured liver decreased by 54 and 50%, respectively. The C-max and AUC would be improved with the alleviation of congestion through the administration of heparin. The study provides a novel insight into the pharmacokinetics of exogenous MSCs in normal and Con A-induced liver injury mice, which provides a framework for optimizing cell transplantation. SIGNIFICANCE STATEMENT Mesenchymal stem/stromal cells (MSCs) are known for their potential as regenerative therapies in treating several diseases, but an insufficient understanding of the pharmacokinetics of MSCs restricts their future application. The current study was the first to elucidate the pharmacokinetics and possible factors, including dosage, species, and derived sources, in a systematic way. The study further revealed that Concanavalin A-induced liver injury significantly prevented cells from entering the injury site, which could be reversed by the diminished congestion achieved by heparin.
资助项目	Organ Reconstruction and Man-ufacturing Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020205] ; National Science Foundation of China[81872927]
WOS关键词	STROMAL CELLS ; IN-VIVO ; INFLAMMATORY RESPONSE ; THERAPY ; MODELS ; MURINE ; TIME ; RAT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000727377400003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299048]
专题	中国科学院上海药物研究所
通讯作者	Li, Hai; Pan, Guoyu
作者单位	1.Univ Chinese Acad Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Haike Rd 501, Shanghai 201203, Peoples R China 3.Shanghai Jiao Tong Univ, State Key Lab Oncogenes & Related Genes, Renji Hosp, Renji Med X Clin Stem Cell Res Ctr,Sch Med, Shanghai, Peoples R China 4.Shanghai Jiao Tong Univ, Dept Gastroenterol, Renji Hosp, Sch Med, Pujian Rd 160, Shanghai 200127, Peoples R China 5.Nanjing Univ Chinese Med, Nanjing, Peoples R China
推荐引用方式 GB/T 7714	Han, Li,Ma, Chenhui,Peng, Huige,et al. Define Mesenchymal Stem Cell from Its Fate: Biodisposition of Human Mesenchymal Stem Cells in Normal and Concanavalin A-Induced Liver Injury Mice[J]. JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,2021,379(2):125-133.
APA	Han, Li.,Ma, Chenhui.,Peng, Huige.,Wu, Zhitao.,Xu, Huiming.,...&Pan, Guoyu.(2021).Define Mesenchymal Stem Cell from Its Fate: Biodisposition of Human Mesenchymal Stem Cells in Normal and Concanavalin A-Induced Liver Injury Mice.JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,379(2),125-133.
MLA	Han, Li,et al."Define Mesenchymal Stem Cell from Its Fate: Biodisposition of Human Mesenchymal Stem Cells in Normal and Concanavalin A-Induced Liver Injury Mice".JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 379.2(2021):125-133.